Lactams are compounds of high interest due to their biological activities, for example well known β-lactams such as some penicillins, cephalosporins and carbapenems have antibacterial activity.
Spirolactams are one particular class of lactams that have shown interesting biological properties. Some spiro-fused azetidinones have been described as having antibacterial activity, see U.S. Pat. No. 4,680,388, or hypocholesterolemic properties, see for example WO 94 17038. Additionally, if these compounds have adequate functionality, they are valuable intermediates towards different families of compounds. The spirolactam ring is the equivalent of an alpha amino or hydroxy aminoacid and opens many possibilities in diastero and/or enantioselective synthesis.
Miyazawa, E. et al. in Heterocycles, vol 59, 1:149-160 “Synthesis of spiro-fused nitrogen heterocyclic compounds via N-methoxy-N-acylnitrenium ions using phenyliodine (III) bis(trifluoroacetate) in trifluoroethanol” describe a process to obtain functionalised spirolactams including some spirodienones.
Kukugawa, Y. e al. in J. Org. Chem. 2003, vol. 68, 6739-6744 “Intramolecular cyclization with nitrenium ions generated by treatment of N-acylaminophthalimides with hypervalent iodine compounds: formation of lactams and spirofused lactams” describes the formation of functionalised spirolactams having diene and dienone functionalities.
The conduritols, aminoconduritols, aminoinositols and their derivatives also possess interesting biological properties, some of them have been shown as being antitumoral and antibiotic. Although some synthetic processes exist for these compounds (See Yong-Uk Kwon et al, J. Org. Chem. 2002, vl. 67, 3327-3338 “Facile syntheses of all possible diastereomers of conduritol and various derivatives of inositol stereoisomers in high enantiopurity from myo-inositol”), there are still difficulties to obtain these compounds or corresponding analogues.
As it is apparent from the above, any efficient process for producing functionalised spirolactam compounds in high yield, with various functionalities, introduced in a controlled and regioselective manner, would be a welcome contribution to the art and will open the door to a variety of biologically active compounds.